The objective of these studies is to understand how cells reversibly reduce the rate of polypeptide chain initiation during their growth cycle and in response to fluctuations in their physiological environment. Regulatory mechanisms in normal and tumor-derived cells in tissue culture will be compared. In addition, we will determine whether physiological conditions which decrease the rate of protein synthesis in vivo can alter the spectrum of proteins synthesized by cells. Using mechanisms previously shown to regulate protein synthesis in cell-free extracts of animal cells as a working hypothesis, we will test whether similar mechanisms actually operate in living cells. These problems will be analyzed by measuring initiation complex formation in intact cells and cell extracts. We will assay for the formation of a translational inhibitor in living cells and analyze its mode of action in rabbit reticulocyte lysates.